Vasopressin Receptor Research Articles

Vasopressin and oxytocin receptors in GtoPdb v.2023.1

Vasopressin (AVP) and oxytocin (OT) receptors (nomenclature as recommended by NC-IUPHAR [94]) are activated by the endogenous cyclic nonapeptides vasopressin and oxytocin. These peptides are derived from precursors which also produce neurophysins (neurophysin I for oxytocin; neurophysin II for vasopressin). Vasopressin and oxytocin differ at only 2 amino acids (positions 3 and 8). There are metabolites of these neuropeptides that may be biologically active [69].

Polymorphisms in Oxytocin and Vasopressin Receptor Genes as a Factor Shaping the Clinical Picture and the Risk of ASD in Males

Autism spectrum disorders (ASD) are a heterogeneous group of disorders affecting virtually every population, regardless of their ethnic or socioeconomic background. Their pathogenesis is multifactorial, based on interactions between genetic and environmental factors. The key symptom of ASD are deficits in social communication, which are the basis of many difficulties in everyday functioning. The aim of the presented study was to analyze the clinical picture of social cognition deficits in boys with autism spectrum disorders and to relate its elements with the frequency of alleles of selected polymorphisms within the oxytocin receptor (OXTR) and vasopressin receptor 1A (AVPR1A) genes. The study included 58 boys with IQ > 90, who were divided into two groups based on a confirmed or excluded ASD diagnosis based on the DSM-5 and ICD-10 criteria and then using the ADOS-2 protocol. The results indicated that polymorphism rs10877969 (T) within the AVPR1a gene was the only one to show a statistically significant association with a higher risk of autism spectrum disorders and has an impact on clinical presentation in the ADOS-2 study, primarily in terms of the social affect subscale. Polymorphisms in the OXTR gene showed no significant association with ASD risk and severity of autistic traits in the ADOS-2 study. In the group of people with ASD and those who are neurotypical, the rs53572 (A) genotype in the OXTR gene significantly increased the severity of the clinical picture of social cognition disorders in reading mind in the eyes test (RMiE) and empathy quotient (EQ) studies.

Natural Peptide Toxins as an Option for Renewed Treatment of Type 2 Vasopressin Receptor-Related Diseases.

The type 2 vasopressin receptor (V2R) is expressed in the kidneys, and it is the keystone of water homeostasis. Under the control of the antidiuretic hormone vasopressin, the V2R ensures vital functions, and any disturbance has dramatic consequences. Despite decades of research to develop drugs capable of activating or blocking V2R function to meet real medical needs, only one agonist and one antagonist are virtually used today. These two drugs cover only a small portion of patients' needs, leaving millions of patients without treatment. Natural peptide toxins known to act selectively and at low doses on their receptor target could offer new therapeutic options.

First reports of clinical effects of transjugular intrahepatic portosystemic shunt in four patients with cirrhotic ascites refractory to tolvaptan

ObjectiveAscites in patients with decompensated cirrhosis can lead to abdominal distention and decrease quality of life. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective agent in the treatment of...

Early Commencement and Long-Term Continuation of Tolvaptan Treatment Attenuate Functional Impairment of Renal Vasopressin V2 Receptors and Improve Clinical Outcomes in Patients with Heart Failure.

Preserved urinary excretion of aquaporin 2, an index for the function of vasopressin V2 receptor (V2-R), has been reported to predict a favorable response of heart failure patients to treatment with tolvaptan. In this study, we investigated the long-term effects of tolvaptan treatment on clinical outcomes and V2-R function in patients with acute decompensated heart failure (ADHF). We enrolled 90 consecutive patients who were hospitalized in Sapporo Medical University Hospital for ADHF and treated with tolvaptan in the BOREAS-ADHF registry and analyzed patients who continued taking tolvaptan after discharge. The effect of tolvaptan treatment on rehospitalization for HF or death was investigated according to whether the V2-R function was preserved (first morning urine osmolarity ≥ 352 mOsm/L, High-Uosm) or impaired (Uosm < 352 mOsm/L, Low-Uosm). During a median follow-up period of 443 days, significantly fewer patients in the High-Uosm group experienced adverse events than did patients in the Low-Uosm group (P < 0.001). Among the patients with High-Uosm, early commencement of tolvaptan administration (on or before day 7 of hospitalization, Early/High-Uosm) significantly reduced adverse events compared to late administration (after day 7 of hospitalization, Late/High-Uosm). Uosm measured during the long-term follow-up period after discharge was significantly reduced compared to that before commencement of tolvaptan administration in the Late/High-Uosm group (from 468 ± 88 to 395 ± 108 mOsm, -18.3 ± 19.6%, P < 0.05) but not in the Early/High-Uosm group (from 478 ± 115 to 455 ± 133 mOsm, -0.50 ± 35.3%, P = 0.66). These findings indicate that early commencement and long-term continuation of tolvaptan treatment attenuate functional impairment of V2-R and improve clinical outcomes in ADHF patients with preserved V2-R function.

AVPR2 is a potential prognostic biomarker and correlated with immune infiltration in head and neck squamous cell carcinoma

PurposeTo explore the potential of AVPR2 in the immunotherapy of head and neck squamous cell carcinoma (HNSCC), thus providing insights into a novel antitumour strategy.MethodsIn this study, we performed a comprehensive analysis of the AVPR2 gene in HNSCC using public datasets from The Cancer Genome Atlas and Gene Expression Omnibus. We explored the potential molecular mechanism of HNSCC in clinical prognosis and tumour immunity from the aspects of gene expression, prognosis, immune subtypes, and immune infiltration.ResultsAVPR2 expression was significantly downregulated in primary HNSCC tissue compared with normal tissue. HNSCC patients with high AVPR2 expression had a better prognosis. Moreover, the results of GSEA showed that immune subtype surface AVPR2 is involved in immune modulation. Furthermore, significant strong correlations between AVPR2 expression and infiltrating immune cells existed in HNSCC, and marker genes of infiltrating immune cells were also significantly related to AVPR2 expression in HNSCC. These results suggest that AVPR2 expression can influence the infiltration of tumour immune cells. Finally, we found that only high levels of B-cell infiltration, rather than those of other immune cells, can predict a longer overall survival in patients with HNSCC. Future studies are needed to explore the role of AVPR2 and tumour-infiltrating B cells in HNSCC.ConclusionsThe AVPR2 gene may be a prognostic biomarker of HNSCC. Moreover, AVPR2 may play a role in HNSCC immune modulation, and the regulation of tumour-infiltrating B cells by AVPR2 may be a key link.

Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management.

Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in the hospital. Syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hypotonic hyponatremia, mediated by nonosmotic release of arginine vasopressin (AVP, previously known as antidiuretic hormone), which acts on the renal V2 receptors to promote water retention. There are a variety of underlying causes of SIAD, including malignancy, pulmonary pathology, and central nervous system pathology. In clinical practice, the etiology of hyponatremia is frequently multifactorial and the management approach may need to evolve during treatment of a single episode. It is therefore important to regularly reassess clinical status and biochemistry, while remaining alert to potential underlying etiological factors that may become more apparent during the course of treatment. In the absence of severe symptoms requiring urgent intervention, fluid restriction (FR) is widely endorsed as the first-line treatment for SIAD in current guidelines, but there is considerable controversy regarding second-line therapy in instances where FR is unsuccessful, which occurs in around half of cases. We review the epidemiology, pathophysiology, and differential diagnosis of SIAD, and summarize recent evidence for therapeutic options beyond FR, with a focus on tolvaptan, urea, and sodium-glucose cotransporter 2 inhibitors.

Arginine vasopressin deficiency and conivaptan (a V1a-V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis.

Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-β (TGF-β) and collagen. Previous work in liver cirrhotic (CCL4 -induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a-V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-β and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.

Novel signalling pathways in nephrogenic syndrome of inappropriate antidiuresis: functional implication of site-specific AQP2 phosphorylation.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease caused by gain-of-function mutations of arginine vasopressin receptor 2 (V2R). Patients with NSIAD are characterized by the inability to excrete a free water load and by inappropriately increased urinary osmolality despite very low levels of plasma vasopressin, resulting in euvolaemic hyponatraemia. To dissect the signalling downstream V2R constitutively active variants, Flp-In T-REx Madin-Darby canine kidney (FTM) cells, stably transfected with V2R mutants (R137L, R137C and F229V) and AQP2-wt or non-phosphorylatable AQP2-S269A/AQP2-S256A, were used as cellular models. All three activating V2R mutations presented constitutive plasma membrane expression of AQP2-wt and significantly higher basal water permeability. In addition, V2R-R137L/C showed significantly higher activity of Rho-associated kinase (ROCK), a serine/threonine kinase previously suggested to be involved in S269-AQP2 phosphorylation downstream of these V2R mutants. Interestingly, FTM cells expressing V2R-R137L/C mutants and AQP2-S269A showed a significant reduction in AQP2membrane abundance and a significant reduction in ROCK activity, indicating the crucial importance of S269-AQP2 phosphorylation in the gain-of-function phenotype. Conversely, V2R-R137L/C mutants retained the gain-of-function phenotype when AQP2-S256A was co-expressed. In contrast, cells expressing the F229V mutant and the non-phosphorylatable AQP2-S256A had a significant reduction in AQP2membrane abundance along with a significant reduction in basal osmotic water permeability, indicating a crucial role of Ser256 for this mutant. These data indicate that the constitutive AQP2 trafficking associated with the gain-of-function V2R-R137L/C mutants causing NSIAD is protein kinaseA independent and requires an intact Ser269 in AQP2 under the control of ROCK phosphorylation. KEY POINTS: Nephrogenic syndrome of inappropriate antidiuresis is caused by two constitutively active variant phenotypes of AVPR2, one sensitive to vaptans (V2R-F229V) and the other vaptan resistant (V2R-R137C/L). In renal cells, all three activating arginine vasopressin receptor 2 (V2R) variants display constitutive AQP2 plasma membrane expression and high basal water permeability. In cells expressing V2R-R137L/C mutants, disruption of the AQP2-S269 phosphorylation site caused the loss of the gain-of-function phenotype, which, in contrast, was retained in V2R-F229V-expressing cells. Cells expressing the V2R-F229V mutant were instead sensitive to disruption of the AQP2-S256 phosphorylation site. The serine/threonine kinase Rho-associated kinase (ROCK) was found to be involved in AQP2-S269 phosphorylation downstream of the V2R-R137L/C mutants. These findings might have clinical relevance for patients with nephrogenic syndrome of inappropriate antidiuresis.

The Effects of SGLT2 Inhibitors on Liver Cirrhosis Patients with Refractory Ascites: A Literature Review.

Decompensated liver cirrhosis is often complicated by refractory ascites, and intractable ascites are a predictor of poor prognosis in patients with liver cirrhosis. The treatment of ascites in patients with cirrhosis is based on the use of aldosterone blockers and loop diuretics, and occasionally vasopressin receptor antagonists are also used. Recent reports suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors may be a new treatment for refractory ascites with a different mechanism with respect to conventional agents. The main mechanisms of ascites reduction with SGLT2 inhibitors appear to be natriuresis and osmotic diuresis. However, other mechanisms, including improvements in glucose metabolism and nutritional status, hepatoprotection by ketone bodies and adiponectin, amelioration of the sympathetic nervous system, and inhibition of the renin-angiotensin-aldosterone system, may also contribute to the reduction of ascites. This literature review describes previously reported cases in which SGLT2 inhibitors were used to effectively treat ascites caused by liver cirrhosis. The discussion of the mechanisms involved is expected to contribute to establishing SGLT2 therapy for ascites in the future.

Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment.

Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease that affects the central nervous system. MS is a heterogeneous disorder of multiple factors that are mainly associated with the immune system including the breakdown of the blood-brain and spinal cord barriers induced by T cells, B cells, antigen presenting cells, and immune components such as chemokines and pro-inflammatory cytokines. The incidence of MS has been increasing worldwide recently, and most therapies related to its treatment are associated with the development of several secondary effects, such as headaches, hepatotoxicity, leukopenia, and some types of cancer; therefore, the search for an effective treatment is ongoing. The use of animal models of MS continues to be an important option for extrapolating new treatments. Experimental autoimmune encephalomyelitis (EAE) replicates the several pathophysiological features of MS development and clinical signs, to obtain a potential treatment for MS in humans and improve the disease prognosis. Currently, the exploration of neuro-immune-endocrine interactions represents a highlight of interest in the treatment of immune disorders. The arginine vasopressin hormone (AVP) is involved in the increase in blood-brain barrier permeability, inducing the development and aggressiveness of the disease in the EAE model, whereas its deficiency improves the clinical signs of the disease. Therefore, this present review discussed on the use of conivaptan a blocker of AVP receptors type 1a and type 2 (V1a and V2 AVP) in the modulation of immune response without completely depleting its activity, minimizing the adverse effects associated with the conventional therapies becoming a potential therapeutic target in the treatment of patients with multiple sclerosis.

Effects of maternal hypertension on cord blood Arginine vasopressin receptor expression.

Arginine vasopressin (AVP) signaling is altered in preeclampsia and physiologic stress. AVP is implicated in fluid homeostasis and cardiovascular (CV) function, which is disrupted in some progeny from preeclamptic pregnancies. However, whether altered fetal AVP signaling occurs in preeclampsia is unknown. Here, we measured CV-related transcripts (e.g., AVP receptors) in cord blood via quantitative PCR. Chronic hypertension decreased AVPR1b, AVPR2, OXTR, LNPEP, and CUL5. AVPR1a, AVPR1b, and AVPR2 were decreased while OXTR was increased in preeclamptic cord blood. In sum, we found prenatal exposure to hypertension in pregnancy alters fetal AVP signaling and may thereby prime offspring CV disease risk.

The role of single nucleotide polymorphisms within genes for oxytocin and vasopressin receptors in the presentation and severity of autistic traits

IntroductionAutism spectrum disorder is a heterogeneous group of disorders that affects virtually every population, regardless of their ethnic or socioeconomic origin. The pathogenesis of ASD is probably multifactorial, based on interactions between genetic and environmental factors. Their key elements are disorders in the field of social communication, establishing and maintaining relationships and the so-called stereotypical and repetitive patterns of interests and activities. However, of the above- mentioned symptoms, the most important are communication disorders, which are the basis for many of the functional difficulties observed in these patients.ObjectivesThe aim of the presented study was to analyze the clinical picture of social cognition deficits in males with autism spectrum disorders, and to link its elements with the frequency of alleles of selected polymorphisms within the OXTR and AVPR1A genes.MethodsThe study included 132 people, 77.5% of whom were male (n = 100). 113 participants (85.6%) were diagnosed with autism spectrum disorders confirmed by the ADOS-2 test conducted by a certified diagnostician. In this group, men constituted 76.1% of the population (n = 77). The remaining 28 people did not have a diagnosis of autism spectrum disorders, and in the ADOS-2 study they obtained the result below the cut-off level. The mean age in the whole group was 14.4 years (95% CI: 13.92-14.93).ResultsA higher frequency of the rs53576 A allele and the rs10877969 C allele could be observed than expected on the basis of the European / world population. In the case of the rs7294536 and rs2254298 polymorphisms, no differences in the distribution of alleles in relation to the expected values were observed. In the network analysis reference allele (T) of SNPs rs10877969 was linked to the higher outcome of the “social affect” domain of ADOS-2 and through it influenced ADOS-2 outcome. All other SNPs did not significantly affect neither domain of ADOS-2. Reference allele (A) of rs53576 was linked with higher odds ratio of clinical diagnosis of ASD in logistic regression. Similarly the rs10877969 polymorphism within the AVPR1a gene significantly shaped the risk of autism spectrum disorders, while in the combined analysis with rs7294536 within the haplotype, the observed effect was significantly stronger.ConclusionsThe studied polymorphisms may constitute an element of larger haplotypes which, depending on the number of mutated alleles, may determine the severity of autism spectrum traits, from the neurotypical population, through people with a broad autism phenotype, to people diagnosed with ASD. Further research is required on the potential clinical application of genotype analysis of the studied polymorphisms and on the exact mechanism of their impact on the risk of ASD and the development of social cognition disorders.Disclosure of InterestNone Declared

Selective Partial Agonism of Vasopressin 1a Receptors In Vitro by OCE-205

Objective To test the selectivity and degree of functional agonism of Ocelot Bio’s dual agonist/antagonist molecule, OCE-205, at the vasopressin 1a receptor (V1aR). Methods Cells expressing human (h) or rat V1a, V1b, V2, or oxytocin receptors (OTR) were incubated with varying concentrations of OCE-205 or with arginine vasopressin (AVP), and responses were measured with fluorescence or reporter gene assays. In addition, human resistance arteries were exposed to increasing concentrations of OCE-205, and the resulting contractility was measured. Results The mean efficacy of OCE-205 at hV1aR was 39% of the maximal possible effect (MPE), with a mean EC50 of 0.71 nM. Above 1 nM OCE-205, the percent maximal possible effect (%MPE) plateaued. The EC50 was much higher at hV1bR (134 nM), hV2R (420 nM), and OTR (6.9 nM), indicating selectivity for hV1aR. Results at rat receptors were similar. OCE-205 produced 40.0% of maximal depolarization-induced contraction, demonstrating functional partial agonism. Conclusion The dual agonist/antagonist structure of OCE-205 thus allows it to act as a highly selective partial agonist at vasopressin V1aR at therapeutically relevant concentrations.

Diagnostic Pitfalls of a Newborn with Congenital Nephrogenic Diabetes Insipidus.

Congenital nephrogenic diabetes insipidus (NDI) is a rare cause of hypernatremia in newborns. Central diabetes insipidus (CDI) is the main differential diagnosis of NDI. NDI responds poorly to desmopressin acetate (DDAVP) treatment while this is the mainstay of CDI management. Therefore, an early and correct diagnosis of NDI is crucial to avoid the complications of inappropriate therapy. Here, we report a newborn with hypernatremia and hypotonic polyuria. The patient was initially responsive but subsequently unresponsive to intranasal DDAVP treatment in regard to urine output and serum sodium levels. A novel hemizygous missense mutation (c.632T>C, p.L211P) in the AVPR2 gene was found both in the baby and his mother, and the diagnosis of congenital NDI was established. After hydrochlorothiazide treatment and hypo-osmolar formula were given, urine volume was decreased, and serum sodium levels were normalized. Early recognition and appropriate management of NDI can prevent complications of hypernatremic dehydration in young infants.

Metabolism-based approaches for autosomal dominant polycystic kidney disease.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) leads to end stage kidney disease (ESKD) through the development and expansion of multiple cysts throughout the kidney parenchyma. An increase in cyclic adenosine monophosphate (cAMP) plays an important role in generating and maintaining fluid-filled cysts because cAMP activates protein kinase A (PKA) and stimulates epithelial chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR). A vasopressin V2 receptor antagonist, Tolvaptan, was recently approved for the treatment of ADPKD patients at high risk of progression. However additional treatments are urgently needed due to the poor tolerability, the unfavorable safety profile, and the high cost of Tolvaptan. In ADPKD kidneys, alterations of multiple metabolic pathways termed metabolic reprogramming has been consistently reported to support the growth of rapidly proliferating cystic cells. Published data suggest that upregulated mTOR and c-Myc repress oxidative metabolism while enhancing glycolytic flux and lactic acid production. mTOR and c-Myc are activated by PKA/MEK/ERK signaling so it is possible that cAMPK/PKA signaling will be upstream regulators of metabolic reprogramming. Novel therapeutics opportunities targeting metabolic reprogramming may avoid or minimize the side effects that are dose limiting in the clinic and improve on the efficacy observed in human ADPKD with Tolvaptan.

Hyponatremia Associated with Congestive Heart Failure: Involvement of Vasopressin and Efficacy of Vasopressin Receptor Antagonists

Hyponatremia is frequently found in patients with congestive heart failure. A reduction in effective circulatory blood volume in a volume-expanded patient with decreased cardiac output is linked to a baroreceptor-mediated non-osmotic release of arginine vasopressin (AVP). The increased production of AVP and salt and water retention in the proximal and distal tubules of the kidney by humoral, hemodynamic, and neural mechanisms increase circulatory blood volume and contribute to hyponatremia. Recent studies have indicated that hyponatremia predicts the short-term and long-term prognosis of heart failure by increasing cardiac death and rehospitalization. In addition, the early development of hyponatremia in acute myocardial infarction also predicts the long-term prognosis of worsening heart failure. AVP V2 receptor antagonism may relieve water retention, but it is unknown whether the V2 receptor inhibitor, tolvaptan, improves the long-term prognosis of congestive heart failure. The newly identified natriuretic factor in renal salt wasting has the potential of improving clinical outcomes when combined with a distal diuretic.

Hyponatremia and Cancer: From Bedside to Benchside

Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. This applies also to cancer patients. Multiple causes can lead to hyponatremia, but most frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis. In cancer patients, this syndrome is mostly secondary to ectopic secretion of arginine vasopressin by tumoral cells. In addition, several chemotherapeutic drugs induce the release of arginine vasopressin by the hypothalamus. There is evidence that hyponatremia is associated to a more negative outcome in several pathologies, including cancer. Many studies have demonstrated that in different cancer types, both progression-free survival and overall survival are negatively affected by hyponatremia, whereas the correction of serum [Na+] has a positive effect on patient outcome. In vitro studies have shown that cells grown in low [Na+] have a greater proliferation rate and motility, due to a dysregulation in intracellular signalling pathways. Noteworthy, vasopressin receptors antagonists, which were approved more than a decade ago for the treatment of euvolemic and hypervolemic hyponatremia, have shown unexpected antiproliferative effects. Because of this property, vaptans were also approved for the treatment of polycystic kidney disease. In vitro evidence indicated that this family of drugs effectively counteracts proliferation and invasivity of cancer cells, thus possibly opening a new scenario among the pharmacological strategies to treat cancer.

Oxytocin antagonist does not disrupt rabbit maternal behavior despite binding to brain oxytocin receptors.

We explored a possible role of oxytocin (OXT) for the onset and maintenance of rabbit maternal behavior by: (a) confirming that a selective oxytocin receptor antagonist (OTA) widely used in rodents selectively binds to OXT receptors (OXTR) in the rabbit brain and (b) determining the effect of daily intracerebroventricular (icv) injections of OTA to primiparous and multiparous does from gestation day 29 to lactation day 3. OTA efficiently displaced the high affinity, selective oxytocin receptor (OXTR) radioligand, 125 I-labeled ornithine vasotocin analog (125 I-OVTA), but was much less effective at displacing the selective V1a vasopressin receptor radioligand, 125 I-labeled linear vasopressin, thus showing high affinity and selectivity of OTA for rabbit OXTR as in rodents. Further, ICV OTA injections did not modify nest-building, latency to enter the nest box, time spent nursing or the amount of milk produced, relative to vehicle-injected does. The percentage of mothers suckling the litter was also similar between both groups, regardless of parity. Together, our results do not support a role of OXT for the initiation or maintenance of rabbit maternal behavior. Future studies are warranted to determine if OXT participates in fine-tuning additional aspects of the maternal ethogram, for example, circadian periodicity of nursing and nest defense.

Tolvaptan for Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in a Child with Corpus Callosum Agenesis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the common causes of euvolemic hyponatremia (serum Na+ < 135 mEq/L) in hospitalized children. It is characterized by increased serum ADH, leading to water retention via its action on V2 receptors in the distal renal tubules.Various conditions such as pain, the postoperative state, drugs, central nervous system infections, tumors, malformations, and pneumonia can predispose a person to SIADH. The conventional treatment of SIADH includes fluid restriction and salt supplementation. Occasionally, this may fail to control hyponatremia, mandating pharmacological therapy. V2-receptor antagonists are an FDA-approved therapy for adults with euvolemic and hypervolemic hyponatremia. However, there is limited experience with their use in the pediatric population. Here, the authors present a girl with corpus callosum agenesis with severe symptomatic hyponatremia due to SIADH who was successfully managed with the V2-receptor antagonist tolvaptan.